Association of TP53 Arg72Pro polymorphism (rs1042522) with bladder cancer risk in the Ukrainian population

  • Ya. M. Mishchuk
  • Ye. V. Kharkivska
  • S. V. Serga
  • S. Ye. Shklyar
  • O. E. Stakhovskyi
  • E. O. Stakhovskyi
  • Yu. V. Vitruk
  • A. A. Kononenko
  • S. V. Demydov
  • L. I. Ostapchenko
  • I. A. Kozeretska

Abstract

Aim. To determine the frequency of TP53 polymorphic variants in bladder cancer patients and define possible association of this polymorphism with a bladder cancer in Ukrainians patients. Methods. The genotypes of TP53 gene at codon 72 were detected by PCR with allele specific primers. We investigated Arg72Pro polymorphism in 114 DNA samples of patients with bladder cancer. The PCR-amplified DNA products were subjected to electrophoresis in 3 % agarose. Results. The distribution of genotypes in group of patients with a bladder cancer was: Arg/Arg – 59.6 % (n=68), Arg/Pro – 40.4 % (n=46), Pro/Pro – 0 % (n=0). Genotype frequencies in patients (χ2=7.28, p=0.0007) weren’t in agreement with Hardy-Weinberg equilibrium. There were significant differences in the frequency of genotypes between the healthy individuals and the cancer group patients. Our result showed that patients with bladder cancer had a significantly higher frequency of Arg/Arg (F=42.7, p<0.05) and a lower frequency of Pro/Arg (F=40.9, p<0.05) compared to controls. Conclusions. Our study allows us to suggest that Arg/Arg polymorphic variant of TP53 is associated with the higher risk of bladder cancer development in the Ukrainian population (OR = 5,6, 95 % CI = 3.19 to 9.34, p < 0.0001).

Keywords: TP53 gene, bladder cancer, polymorphism Arg72Pro, Ukrainian population.

References

Murta-Nascimento C., Schmitz-Drager B.J., Zeegers M.P., Steineck G., Kogevinas M., Real F.X., Malats N. Epidemiology of urinary bladder cancer: from tumor development to patient's death. World J. Urol. 2007. Vol. 25. P. 285–295. doi: 10.1007/s00345-007-0168-5.

McConkey D.J., Lee S., Choi W., Tran M., Majewski T., Siefker-Radtke A., Dinney C., Czerniak B. Molecular genetics of bladder cancer: emerging mechanisms of tumor initiation and progression. Urol. Oncol. 2010. Vol. 28. P. 429–440. doi: 10.1016/j.urolonc.2010.04.008.

Pineda S., Milne R.L., Calle M.L., Rothman N., Lopez de Maturana E., Herranz J., Kogevinas M., Chanock S.J., Tardon A., Marquez M., Guey L.T., Garcia-Closas M., Lloreta J., Baum E., Gonzalez-Neira A., Carrato A., Navarro A., Silverman D.T., Real F.X., Malats N. Genetic variation in the TP53 pathway and bladder cancer risk. a comprehensive analysis. PLoS One. 2014. Vol. 9. P. 1–8. doi: 10.1371/journal.pone.0089952.

Denisov E.V., Cherdyntseva N.V., Litviakov N.V., Malinovskaya E.A., Babyshkina N.N., Belyavskaya V.A., Voevoda M.I. TP53 gene polymorphism in cancer risk: the modulating effect of ageing, ethnicity and TP53 somatic abnormalities. In: Cheng Y, editor. Tumor suppressor genes. Rijeka, Croatia: InTech, 2012. P. 79–110. URL: http://www.intechopen.com/books/tumor-suppressor-genes/tp53-gene-polymorphisms-in-cancer-risk-the-modulating-effect-of-ageing-ethnicity-and-tp53-somatic-ab (Last accessed: 27.02.2018).

Lin H.Y., Yang M.C., Huang C.H., Wu W.J., Yu T.J., Lung F.W. Polymorphisms of TP53 are markers of bladder cancer vulnerability and prognosis. Urol Oncol. 2013. Vol. 31. P. 1231–1241. doi: 10.1016/j.urolonc.2011.11.031.

Lin H.Y., Huang C.H., Wu W.J., Chang L.C., Lung F.W. TP53 codon 72 Gene Polymorphism Paradox in Associated with Various Carcinoma Incidences, Invasiveness and Chemotherapy Responses. Int J Biomed Sci. 2008. Vol. 4. P. 248–254.

Khan M.H., Khalil A., Rashid H. Evaluation of the p53 Arg72Pro polymorphism and its association with cancer risk: a HuGE review and meta-analysis. Genet. Res. (Camb). 2015. Vol. 97. P. 1–11. doi: 10.1017/S0016672315000075.

Dumont P., Leu J.I., Della Pietra A.C. 3rd, George D.L., Murphy M. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet. 2003. Vol. 33. P. 357–365. doi: 10.1038/ng1093.

Pim D., Banks L. p53 polymorphic variants at codon 72 exert different effects on cell cycle progression. Int J Cancer. 2004. Vol. 108. P. 196–199. doi: 10.1002/ijc.11548.

Siddique M., Sabapathy K. Trp53-dependent DNA-repair is affected by the codon 72 polymorphism. Oncogene. 2006. Vol. 25. P. 3489–3500. doi: 10.1038/sj.onc.1209405.

Soulitzis N., Sourvinos G., Dokianakis D.N., Spandidos D.A. p53 codon 72 polymorphism and its association with bladder cancer. Cancer Lett. 2002. Vol. 179. P. 175–183.

Prescott J.L., Montie J., Pugh T.W., McHugh T., Veltri R.W. Clinical sensitivity of p53 mutation detection in matched bladder tumour, bladder wash, and voided urine specimens. Cancer. 2001. Vol. 91. P. 21–27.

Zhang R., Chen W., Zhang W., Jiang Q., Liu C., Lin Y., Hu Z., Yu S., Xu G. Genetic polymorphisms of p53 codon 72 and bladder cancer susceptibility: a hospitalbased case-control study. Genet. Test. Mol. Biomarkers. 2011. Vol. 15. P. 337–341. doi: 10.1089/gtmb.2010.0230.

Lin H.Y., Huang C.H., Yu T.J., Wu W.J., Yang M.C., Lung F.W. p53 codon 72 polymorphism was associated with vulnerability, progression, but not prognosis of bladder cancer in a Taiwanese population: an implication of structural equation modeling to manage the risks of bladder cancer. Urol. Int. 2011. Vol. 86. P. 355–360. doi: 10.1159/000323599.

Xu T., Xu Z.C., Zou Q., Yu B., Huang X.E. P53 Arg72Pro polymorphism and bladder cancer risk- meta-analysis evidence for a link in Asians but not Caucasians. Asian Pac. J. Cancer Prev. 2012. Vol. 13. P. 2349–2354.

Borkowska E., Traczyk M., Pietrusinski M., Matych J., Kaluzewski B. The significance of p53 gene codon 72 and 213 polymorphisms in urinary bladder cancer in Central Poland. Cent. European J. Urol. 2010. Vol. 63. P. 9–13.

Mabrouk I., Baccouche S., El-Abed R., Mokdad-Gargouri R., Mosbah A., Saïd S., Daoud J., Frikha M., Jlidi R., Gargouri A. No evidence of correlation between p53 codon 72 polymorphism and risk of bladder or breast carcinoma in Tunisian patients. Ann. N. Y. Acad. Sci. 2003. Vol. 1010. P. 764–770.

Jiang D.K., Ren W.H., Yao L., Wang W.Z., Peng B., Yu L. Meta-analysis of association between TP53 Arg72Pro polymorphism and bladder cancer risk Urology. 2010. Vol. 76. P. 765. doi: 10.1016/j.urology.2010.04.044.

Baek W.K., Cho J.W., Suh S.I., Suh M.H., Shin D.H., Cho C.H., Lee T.S., Cha S.D. p53 codon 72 polymorphism and risk of cervical carcinoma in Korean women. Korean Med. Sci. 2000. Vol. 15. P. 65–67. doi: 10.3346/jkms.2000.15.1.65.

Atramentova L.A., Utevskaia O.M. Statistical methods in the biology. Horlovka: Likhtar. 2008. 248 s.

Trikalinos T.A., Salanti G., Khoury M.J., Ioannidis J.P. Impact of Violations and Deviations in Hardy-Weinberg Equilibrium on Postulated Gene-Disease Associations. Am. J. Epidemiol. 2006. Vol. 163. P. 300–309. doi: 10.1093/aje/kwj046.

Mishchuk Y.M., Serga S.V., Koliada O.K., Ostapchenko L.I., Demydov S.V., Kozeretska I.A. TP53 codon 72 polymorphic variants (Rs1042522) frequency in the Ukrainian population. Problems of radiation medicine and radiobiology. 2015. Vol. 20. P. 414–419.

Mabrouk I., Baccouche S., El-Abed R., Mokdad-Gargouri R., Mosbah A., Saïd S., Daoud J., Frikha M., Jlidi R., Gargouri A. No evidence of correlation between p53 codon 72 polymorphism and risk of bladder or breast carcinoma in Tunisian patients. Ann N Y Acad Sci. 2003. Vol. 1010. P. 764–770.

Soulitzis N., Sourvinos G., Dokianakis D.N., Spandidos D.A. p53 codon 72 polymorphism and its association with bladder cancer. Cancer Lett. 2002. Vol. 179. P. 175–183.

Smith N.D., Rubenstein J.N., Eggener S.E., Kozlowski J.M. The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol. 2003. Vol. 169. P. 1219–1228. doi: 10.1097/01.ju.0000056085.58221.80

Yang Z., Nie S., Zhu H., Wu X., Jia S., Luo Y., Tang W. Association of p53 Arg72Pro polymorphism with bladder cancer: a meta-analysis. Gene. 2013. Vol. 512. P. 408–413. doi: 10.1016/j.gene.2012.09.085.

Siddique M., Sabapathy K. Trp53-dependentDNA-repair is affected by the codon 72 polymorphism. Oncogene. 2006. Vol. 25. P. 3489–3500. doi: 10.1038/sj.onc.1209405